Efficacy of Long-Term Tenofovir-Based Therapy in Chronic Hepatitis B Patients with Previous Nucleos(t)ide Analogues Treatment Experience

( Na Eun Lee ),( Hong Seon Son ),( Sung Hoon Choi ),( Chang Hun Lee ),( Seung Young Seo ),( Seong Hun Kim ),( Sang Wook Kim ),( Seung Ok Lee ),( Soo Teik Lee ),( Dae Ghon Kim ),( In Hee Kim ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Tenofovir disoproxil fumarate (TDF) is considered as the preferred treatment option for chronic hepatitis B (CHB) patients with treatment failure or resistance to prior nucleos(t)ide analogues (NAs) treatment. We investigated the efficacy of long-term TDF-based therapy in CHB patients with previous NAs-experience. Methods: This study included total 251 patients who had previous history of NAs therapy and were treated with TDF mono (n=173) or TDF combined with other NA (n=78) from August 2012 to March 2017. Virologic response (VR) was defined as undetectable serum HBV DNA by PCR (<20 IU/mL). Results: Mean age of patients was 49.3 years, median duration of TDF therapy was 27.2 months, 75.7% were HBeAg-positive, and median HBV DNA was 3.7 log10IU/mL. The cumulative rates of VR were 188/244 (77.0%), 180/211 (85.3%), and 146/161 (90.7%) at 12, 24, and 36 months, respectively. Multivariate analysis showed that body mass index (OR 0.77, 95% CI 0.61-0.95, p=0.0189) and duration of TDF therapy (OR 1.09, 95% CI 1.02-1.18, p=0.0221) was significantly associated with VR. TDF monotherapy, HBeAg-positivity, platelet count, serum albumin was associated with VR in the univariate analysis, but not significant in the multivariate analysis. In relation to renal safety, patients showed renal impairment (7, 3.0%), mild hypophosphatemia (15, 7.2%), severe hypophosphatemia (1, 0.4%). Conclusions: Long-term TDF-based therapy demonstrated highly effective in viral suppression and relatively favorable renal safety in CHB patients with previous NA-experience. The body mass index and duration of TDF therapy was independent factors associated with VR.

Comparison of Virologic Response and Renal Safety of Long-Term Antiviral Therapy with Tenofovir and Entecavir in Naive Patient with Chronic Hepatitis B

( Hong Seon Son ),( Sung Hoon Choi ),( Na Eun Lee ),( Chang Hun Lee ),( Seung Young Seo ),( Seong Hun Kim ),( Sang Wook Kim ),( Seung Ok Lee ),( Soo Teik Lee ),( Dae Ghon Kim ),( In Hee Kim ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Tenofovir (TDF) entecavir (ETV) are considered as the preferred treatment options for treatment-naïve chronic hepatitis B (CHB) patients. We compared the virologic response and renal safety of long-term TDF versus ETV therapy in naïve CHB patients. Methods: This retrospective study included total 432 patients who were treated with TDF (n=205) or ETV (n=227) from August 2012 to March 2017. Virologic response (VR) was defined as undetectable serum HBV DNA by PCR (<20 IU/mL). Results: Mean age of patients, sex, baseline serum levels of AST, ALT, creatinine, and HBV DNA were not significantly different between TDF and ETV groups. The cumulative rates of VR between TDF and ETV groups were 71.6% vs. 61.8% (p=0.477), 88.1% vs. 79.6% (p=0.058), and 84.8% vs. 83.7% (p=0.966) at 1, 2, and 3 years, respectively. The cumulative rates of genotypic resistance between TDF and ETV groups were 0% vs. 0%, 0% vs. 1.5% (p=0.404), and 0% vs. 2.2% (p=0.447) at 1, 2, and 3 years, respectively. Incidences of renal impairment and hypophosphatemia during treatment up to 3 years were not significantly different between two groups. Multivariate analysis showed that HBeAg-positivity (OR 0.27, 95% CI 0.12-0.58, p=0.0012) and serum HBV DNA at 1 year 2000 IU/mL (OR 0.09, 95% CI 0.03-0.25, p<0.0001) were significantly associated with VR. Conclusions: Long-term TDF and ETV treatments appear to have similar virologic response and renal safety in naïve CHB patient. However, long-term ETV therapy might to be associated with genotypic resistance in 2.2% up to 3 years, while none of patients on TDF therapy did.

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

관여도에 따른 광고 메시지구조에서의 양상(modality) 효과와 광고프레임별 영향력 효과

나운봉,손영석,김충현 한국방송광고공사 2009 광고연구 Vol.0 No.83

본 연구에서는 기존에 진행되어온 양상(modaity)에 대한 연구를, 광고 메시지 차원에서 시각적 및 청각적 요인의 영향력에 대한 소비자들의 태도 및 행동적 변수의 영향력을 측정하여 수행하였다. 이를 위해서 제품 관여도를 조절 변수로 사용하였으며, 광고 메시지를 프레임별로 접근하여 각각의 프레임에서의 두 요인의 역할과 영향력에 대해서 평가하였다. 연구결과, 청각적 요소가 시각적 요인에 비해서 소비자들의 태도 및 행동적 변수에 대한 영향력에 더 큰 영향력을 미치는 것으로 나타났으며, 15초의 광고시간동안 시계열적인 프레임으로 구분하는 경우에 단계별로 시각적 요인과 청각적 요인의 광고 영향력이 차이가 존재하는 것으로 나타났다. 15초의 광고시간동안 시계열적인 기승전결에 따른 4단계 프레임으로 구분하여 분석하는 경우에, 단계별로 시각적 요인과 청각적인 요인의 광고 영향력이 차이가 존재하는 것으로 나타났다. 즉 양상(modality)에 따라서 광고 메시지의 초기단계에서는 시각적 요소가 강하게 작용하는 시각적 초기효과를 나타내었으며, 후반으로 진행될수록 청각적 최근효과를 보이는 것으로 나타났다. 즉 방송광고 구조에서 초기에는 시각적 초기효과를 보이는 것으로 나타났다. 즉 방송광고 구조에서 초기에는 시각적 초기효과(visual-primacy effect), 후반에는 청각적 최근효과(auditory-recency effect)의 패턴으로 나타남을 확인할 수 있었다. The stepwise effect of visual and auditory element of advertising message toward consumer's attitude and behavior is illuminated on this research. For the purpose of revealing this modality effect, the advertising stimulus is framed by 4 stages, according to the Korean traditional plot theory, as is identified on the narrative structure. Also, the product involvement is adopted as moderate variable, In summary, the result shows auditory element is predominant to the visual element on the context of advertising, especially, it affects attitude and behavioral variables such as liking, understanding and purchase intention. For the short time of 15 seconds, there resides plot in the advertising narratives, also. this phenomenon of visual-primacy effect and auditory-recency effect is revealed.

전신성 홍반성 낭창의 임상적 고찰

신영태,김종학,장윤경,양종오,구영선,강민규,황평주,나기량,이강욱,서광선 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

The epidemiology, diagnostic criteria, clinical features, symptoms and signs laboratory findings, kidney pathology, and clinicopathologic correlation of systemic lupus erythematosus(SLE) were analyzed. The 63 patients studied were managed at the Department of Internal medicine, CNUH, from January 1983 to December 1997. Kidney biopsy was performed in 53 patients out of 63 patients with SLE. The results were as follows: 1. The ratio of male to female was 1:26. They were 12 to 71 years old and mean age was 32.1 years old. The peak age incidence was 4th decades(30%). 2. The most frequent chief complaint on admission was generalized edema. Most patients complain two or more symptoms. 3. Immunologic and renal disorders were the most frequently observed in the ARA criteria of SLE. And the positive ANA, hematologic disorder, malar rash, and arthritis, were observed in order of frequency. 4. Among the 53 patients with renal biopsy, 30 patients revealed class Ⅳ lupus nephritis(56%), class II in 12 patients(23%), class V in 8 patients(15%) and class III in 2 patients(6%). 5. The cases of lupus nephritis represented as nephrotic syndrome were high in the class IV with 68% and class V with 86%. 6. Of 30 patients who can be followed up, 5 patients resulted in death(17 % of mortality). They "were 14 to 57 years old and mean age was 28 years old. Follow up duration were from 1 month to 6 years and 3 months, and mean duration was 1 year and 1 month, but 3 cases 7. The causes of death were as follows: Two cases were due to seizure and coma resulted from CNS involvement. One was sepsis due to miliary the & pneumonia. One was dilated cardiomyopathy and heart failure due to cardiac ac involvement. And the other one was sepsis and acute renal failure resulted from cellulitis. 8. Prednisolone was used in all patients basically, and methyl-prednisolone pulse therapy, antimalarials and alkylating agents were used in some cases. In the cases of combined therapy, the activity of SLE was well controlled.

염색체 위치 특이적 삽입과 안정적인 유전자 발현을 유도하는 플라스미드 백터의 제작

문영준,강윤성,최지혜,손진숙,민나영,이광호 中央大學校 基礎科學硏究所 2002 基礎科學硏究所 論文集 Vol.16 No.-

Insertion of reporter constructs into the mammalian genome leads to variable gene expression due to position effects at the site of integration. This random integration has limited the gene therapy of human genetic disorders by its undesirable effects. We report here the newly constructed plasmid vector(pIRES-neo-YJ) based on the concepts of homologous recombination and position-independent promoter enhancing of beta-globin matrix attachment region(Glb-MAR). chromosome 7 centromere-specific alpha satellite(alphoid) DNA sequence was cloned into pIRES-neo-YJ for homologous recombination of the cloned gene with the centromeric region of chromosome 7, which is genetically silent. Beta Glb-MAR sequence that allows high levels of transcription independent of the chromosomal site of integration was also inserted into pIRES-neo-YJ to ensure the stable and higher expression of the cloned genes. We expect that pIRES-neo-YJ would provide a valuable tool to eliminate random integration of cloned genes into the undesirable chromosomal region and their short-lived expression which often encounters during the construction of transgenic animals and human gene therapy.

신이식에서 이식신의 생존분석

오선미,김종학,황평주,구영선,강민규,나기량,김종섭,김성숙,이강욱,신영태,설종구,배진선,손기섭 충남대학교 의과대학 지역사회의학연구소 1997 충남의대잡지 Vol.24 No.2

To investigate the prognostic factors for the survival of transplanted kidney in patients with end-stage renal failure, 59 cases of renal transplantation from September 1986 to Feburary 1997 in Chungnam National University Hospital were analyzed retrospectively. The results were as follows: 1)The mean age of recipients was 33.8 years and that of doners was 38.9 years. The male to female ratio of recipients was 2.5:1, and that of donors was 1.03:1 2) Living related donore(LRD) were 79.6% and living non-related donors were 20.3%. The HLA-identical donors(ID) in LRD were 18.7% and HLA-haploidentical donors(HID) were 61.0%. In living non-related donors(LNRD), mean matched HLA-AB antigens were 1.56 and mean matched HLA-DR antigens were 0.56. 3) The average 5-year patient survival fate was 94%, and average 5-year graft survival rate was 70%. The 5-year graft survival fate of HLA-ID was 100%, and those HLA-HID and LNR were 70% and 36% respectively. 4) Total 33 episodes of acute rejection were found in 45.8% of transplanted patients. The number of acute rejection episode did not show significant difference between LRD and LNRD(P > 0.05). There was no significant difference in MLC between two groups(p > 0.05). 5) In comparison between the 18 patients who lost their graft function in 5 years and 17 patients who are maintaining graft function for more than 5 years, MLC was significantly lower in patients with functioning graft than of patients with non-functioning graft (p < 0.05). The number of rejection episode was also lower in patients with functioning graft than that of the patients with non-functioning graft(p < 0.05). However, there were no significant difference in recepient and donor age and history of pre-transplantation donor specific transfusion between two groups. With the results above, we can speculate that adequate donor selection according to good matched HLA typing and low MLC is very important for graft survival in renal transplantation. Prevention and treatment of acute rejection in renal transplantation is also na important factor for graft survival.

Gitelman 증후군 환자에서 면역조직화학법으로 확인한 원위세관 sodium-chloride cotransporter (NCCT)의 결손

장혜련 ( Hye Ryoun Jang ),허남주 ( Nam Ju Heo ),손민정 ( Min Jung Son ),이재욱 ( Jay Wook Lee ),이정환 ( Jeong Hwan Lee ),전은실 ( Un Sil Jeon ),신성준 ( Sung Jun Shin ),나기영 ( Ki Young Na ),주권욱 ( Kwon Wook Joo ),이정상 ( Jun 대한내과학회 2005 대한내과학회지 Vol.69 No.6

목적 : Gitelman 증후군은 저포타시움혈증, 대사성 알칼리증, 고레닌혈증, 고알도스테론혈증, 요 중 칼슘 배설의 저하 및 저마그네슘혈증을 특징으로 하는 유전성 질환이다. 이는 원위세관 sodium-chloride cotransporter (NCCT)의 유전자 돌연변이에 의하여 발생하는 것으로 알려져 있으나 사람의 신조직에서 NCCT 결손이 증명된 바는 없었다. 방법 : 저자들은 임상적으로 Gitelman 증후군이 의심되는 환자에서 이뇨제를 이용한 신청소율 검사와 유전자 검사를 시행하였고, 이를 통하여 감별진단한 Gitelman 증후군 환자의 신조직에서 인간 NCCT에 대한 토끼 다클론 항체를 이용한 면역조직화학법을 시행하였다. 신세포암으로 신적출술을 시행 받은 환자의 정상 신조직과 전해질 이상이 없었던 사구체신염 환자의 신조직을 각각 정상 대조군과 질환 대조군으로 하였다. 결과 : 대상 환자는 저포타시움혈증과 대사성 알칼리증, 저마그네슘혈증 및 요 중 칼슘 배설의 저하를 보였다. Bartter 증후군과 감별을 위하여 furosemide 및 hydrochlorothiazide를 이용한 신청소율 검사를 시행하였다. 수분 부하를 시행한 기저치(86.1%)에 비해서 furosemide를 투여한 후 distal fractional chloride reabsorption이 감소하였으나(9.7%) hydrochlorothiazide 투여 후에는 변화가 없었다(81.4%). 유전자 검사 결과 SLC12A3 유전자의 돌연변이(S967F)가 발견되었다. 신조직에서 면역조직화학법을 시행한 결과 정상 및 질환 대조군에서는 원위세관 세포의 내강 막 쪽에 NCCT가 뚜렷이 염색되었으나, Gitelman 증후군에서는 원위세관 세포의 NCCT에 대한 면역 반응성이 관찰되지 않았다. 반면에 Na/K-ATPase, Na-K-2Cl cotransporter, calbindin-D28K는 대조군과 대상 환자의 신조직에서 모두 관찰되었다. 결론 : 기능적 검사로 진단된 Gitelman 증후군 환자의 신조직에서 NCCT의 결함을 면역조직화학법으로 확인하였다. Background : Gitelman`s syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. It is known to be caused by a mutation of SLC12A3 gene coding the sodium-chloride cotransporter (NCCT) in the distal tubule. The defect of NCCT in human renal tissues has not been investigated, and we tested whether the defect of NCCT can be detected in renal tissue of a patient with Gitelman`s syndrome by using immunohistochemistry. Methods : In an adult patient with Gitelman`s syndrome, blood and urine samples were collected for measurement of biochemical parameters. Renal clearance study and gene analysis were performed. Immunohistochemistry was performed on the renal tissue of the patient using a rabbit polyclonal antibody directed against a synthetic peptide corresponding to a portion in the amino terminal tail for human NCCT. Normal human renal tissues from surgical nephrectomy due to renal cell carcinoma and renal biopsy tissues from patients with glomerulonephritis but without any electrolyte disturbance were used as controls. Results : The patient had hypokalemic metabolic alkalosis, hypocalciuria and hypomagnesemia. Renal clearance study revealed a decrease in distal fractional chloride reabsorption after the administration of furosemide. SLC12A3 gene mutation (S967F) was found by direct sequencing method. Immunohistochemistry showed the absence of NCCT staining in the renal tissue of the patient. On the other hand, the immunostaining of other transporters was all positive in renal tissues from both Gitelman`s syndrome patients and controls. Conclusions : We report the absence of intact NCCT in the renal tissue of a Gitelman`s syndrome patient.(Korean J Med 69:642-650, 2005)

The Desulfuration Activity Effect of Organic Wastes on the Biomarker, Cytochrome P<SUB>450</SUB> Extracted from Earthworm, Eisenia fetida

Na, Young Eun,Hae Son Bang,Kee Kyung Kang,Min Sun Han,Young Joon Ahn 한국토양비료학회 2005 한국토양비료학회 학술발표회 초록집 Vol.2005 No.9

Optical Orbit Determination of a Geosynchronous Earth Orbit Satellite Effected by Baseline Distances between Various Ground-based Tracking Stations II: COMS Case with Analysis of Actual Observation Data

Son, Ju Young,Jo, Jung Hyun,Choi, Jin,Kim, Bang-Yeop,Yoon, Joh-Na,Yim, Hong-Suh,Choi, Young-Jun,Park, Sun-Youp,Bae, Young Ho,Roh, Dong-Goo,Park, Jang-Hyun,Kim, Ji-Hye The Korean Space Science Society 2015 Journal of Astronomy and Space Sciences Vol.32 No.3

We estimated the orbit of the Communication, Ocean and Meteorological Satellite (COMS), a Geostationary Earth Orbit (GEO) satellite, through data from actual optical observations using telescopes at the Sobaeksan Optical Astronomy Observatory (SOAO) of the Korea Astronomy and Space Science Institute (KASI), Optical Wide field Patrol (OWL) at KASI, and the Chungbuk National University Observatory (CNUO) from August 1, 2014, to January 13, 2015. The astrometric data of the satellite were extracted from the World Coordinate System (WCS) in the obtained images, and geometrically distorted errors were corrected. To handle the optically observed data, corrections were made for the observation time, light-travel time delay, shutter speed delay, and aberration. For final product, the sequential filter within the Orbit Determination Tool Kit (ODTK) was used for orbit estimation based on the results of optical observation. In addition, a comparative analysis was conducted between the precise orbit from the ephemeris of the COMS maintained by the satellite operator and the results of orbit estimation using optical observation. The orbits estimated in simulation agree with those estimated with actual optical observation data. The error in the results using optical observation data decreased with increasing number of observatories. Our results are useful for optimizing observation data for orbit estimation.